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1.
Aging Cell ; : e14190, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38725282

ABSTRACT

Aging is associated with low-grade inflammation that increases the risk of infection and disease, yet the underlying mechanisms remain unclear. Gut microbiota composition shifts with age, harboring microbes with varied immunogenic capacities. We hypothesized the gut microbiota acts as an active driver of low-grade inflammation during aging. Microbiome patterns in aged mice strongly associated with signs of bacterial-induced barrier disruption and immune infiltration, including marked increased levels of circulating lipopolysaccharide (LPS)-binding protein (LBP) and colonic calprotectin. Ex vivo immunogenicity assays revealed that both colonic contents and mucosa of aged mice harbored increased capacity to activate toll-like receptor 4 (TLR4) whereas TLR5 signaling was unchanged. We found patterns of elevated innate inflammatory signaling (colonic Il6, Tnf, and Tlr4) and endotoxemia (circulating LBP) in young germ-free mice after 4 weeks of colonization with intestinal contents from aged mice compared with young counterparts, thus providing a direct link between aging-induced shifts in microbiota immunogenicity and host inflammation. Additionally, we discovered that the gut microbiota of aged mice exhibited unique responses to a broad-spectrum antibiotic challenge (Abx), with sustained elevation in Escherichia (Proteobacteria) and altered TLR5 immunogenicity 7 days post-Abx cessation. Together, these data indicate that old age results in a gut microbiota that differentially acts on TLR signaling pathways of the innate immune system. We found that these age-associated microbiota immunogenic signatures are less resilient to challenge and strongly linked to host inflammatory status. Gut microbiota immunogenic signatures should be thus considered as critical factors in mediating chronic inflammatory diseases disproportionally impacting older populations.

2.
Biomolecules ; 14(4)2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38672435

ABSTRACT

Obesity is a fast-growing epidemic affecting more than 40% of the US population and leads to co-morbidities such as type 2 diabetes and cancer. More importantly, there is a rapid increase in childhood obesity associated with obesity in parents. Further, offspring are encoded with approximately half of their genetic information from the paternal side. Obesity in fathers at the preconceptional period likely influences the intergenerational development of obesity. This study focuses on the role of fish oil supplementation as a non-pharmacological intervention in fathers and its impact on childhood obesity using animal models. Male mice were fed a low-fat diet or high-fat diet with or without fish oil for 10 weeks and mated with female mice on a chow diet. Offspring were then continued on a chow diet until 8 or 16 weeks. In vivo insulin tolerance was tested to assess the metabolic health of offspring. Further, adipose tissue was harvested upon sacrifice, and genetic markers of inflammation and lipid metabolism in the tissue were analyzed. Offspring of males supplemented with fish oil showed lower body weight, improved insulin tolerance, and altered inflammatory markers. Markers of fatty acid oxidation were higher, while markers of fatty acid synthesis were lower in offspring of fathers fed fish oil. This supports fish oil as an accessible intervention to improve offspring metabolic health.


Subject(s)
Adipose Tissue , Diet, High-Fat , Fish Oils , Animals , Fish Oils/pharmacology , Male , Mice , Female , Adipose Tissue/metabolism , Adipose Tissue/drug effects , Diet, High-Fat/adverse effects , Obesity/metabolism , Mice, Obese , Lipid Metabolism/drug effects , Dietary Supplements , Mice, Inbred C57BL , Insulin Resistance , Disease Models, Animal , Pregnancy
3.
Nutrients ; 15(24)2023 Dec 08.
Article in English | MEDLINE | ID: mdl-38140297

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is a serious public health concern, which calls for appropriate diet/nutrition intervention. Fish oil (FO) has several benefits in reducing obesity, but its intergenerational role in reducing the effects of paternal obesity has not been established. Hence, we hypothesized that FO supplementation to an obese father during the pre-conceptional period could improve the metabolic health of the offspring, specifically in the liver. Three groups of male mice were fed with a low-fat (LF), high-fat (HF), or high-fat diet supplemented with FO (HF-FO) for 10 weeks and were then allowed to mate with female mice fed a chow diet. Offspring were sacrificed at 16 weeks. The liver tissue was harvested for genomic and histological analyses. The offspring of HF and HF-FO fathers were heavier compared to that of the LF mice during 9-16 weeks. The glucose tolerance of the offspring of HF-FO fathers were significantly improved as compared to the offspring of HF fathers. Paternal FO supplementation significantly lowered inflammation and fatty acid synthesis biomarkers and increased fatty acid oxidation biomarkers in the offspring liver. In summary, FO supplementation in fathers shows the potential to reduce metabolic and cardiovascular diseases through genetic means in offspring.


Subject(s)
Fish Oils , Non-alcoholic Fatty Liver Disease , Male , Female , Mice , Animals , Humans , Fish Oils/pharmacology , Fish Oils/metabolism , Obesity/prevention & control , Obesity/metabolism , Dietary Supplements , Diet, High-Fat/adverse effects , Liver/metabolism , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/prevention & control , Non-alcoholic Fatty Liver Disease/metabolism , Fathers , Biomarkers/metabolism , Fatty Acids/metabolism , Mice, Inbred C57BL
4.
Front Cardiovasc Med ; 8: 696812, 2021.
Article in English | MEDLINE | ID: mdl-34368253

ABSTRACT

Maternal obesity has many implications for offspring health that persist throughout their lifespan that include obesity and cardiovascular complications. Several different factors contribute to obesity and they encompass interplay between genetics and environment. In the prenatal period, untreated obesity establishes a foundation for a myriad of symptoms and negative delivery experiences, including gestational hypertensive disorders, gestational diabetes, macrosomia, and labor complications. However, data across human and animal studies show promise that nutritional interventions and physical activity may rescue much of the adverse effects of obesity on offspring metabolic health. Further, these maternal interventions improve the health of the offspring by reducing weight gain, cardiovascular disorders, and improving glucose tolerance. Mechanisms from animal studies have also been proposed to elucidate the signaling pathways that regulate inflammation, lipid metabolism, and oxidative capacity of the tissue, ultimately providing potential specific courses of treatment. This review aims to pinpoint the risks of maternal obesity and provide plausible intervention strategies. We delve into recent research involving both animal and human studies with maternal interventions. With the increasing concerning of obesity rates witnessed in the United States, it is imperative to acknowledge the long-term effects posed on future generations and specifically modify maternal nutrition and care to mitigate these adverse outcomes.

5.
JNMA J Nepal Med Assoc ; 58(232): 1056-1060, 2020 Dec 31.
Article in English | MEDLINE | ID: mdl-34506371

ABSTRACT

INTRODUCTION: Epistaxis is a common medical emergency with 5% to 15% of patients admitted for epistaxis will require surgical management as nasal packing has high failure rates. A modern endoscopic technique like Endoscopic Sphenopalatine Artery Ligation has increased in popularity for managing intractable posterior epistaxis. It has less complication and a high success rate. The study conducted to estimate the success rate of Endoscopic Sphenopalatine Artery Ligation of refractory posterior epistaxis among admitted patients in a tertiary care hospital. METHODS: This is a descriptive cross-sectional study conducted from June 2019 to June 2020 at the Department of Otorhinolaryngology, Nobel Medical College and Teaching Hospital among the patient with refractory posterior epistaxis with the help of retrospective data. A convenient sampling method was used. These patients underwent endoscopic sphenopalatine artery cauterization for recurrent/intractable posterior epistaxis. Ethical clearance was taken from the Institutional Review Board. Data were analyzed in Statistical Package for the Social Sciences. RESULTS: Out of the total patient with refractory posterior epistaxis who underwent Endoscopic Sphenopalatine Artery Ligation, the overall success rate was 39 (95.12%). Among them, 25 (60.97%) males and 16 (39.02%) females underwent endoscopic sphenopalatine artery ligation. Twenty (48.78%) of them were unilateral whilst 21 (51.21%) were bilateral disease. About 2 (4.8%) cases had re-bleeding within 48 hours which was managed conservatively. Hypertension was found to be the most common comorbid condition followed by diabetes, chronic kidney. CONCLUSIONS: From our study, we conclude that the success rate for Endoscopic Sphenopalatine Artery Ligation in a patient with refractory posterior epistaxis was high.


Subject(s)
Epistaxis , Maxillary Artery , Arteries , Cross-Sectional Studies , Epistaxis/etiology , Epistaxis/surgery , Female , Humans , Ligation , Male , Retrospective Studies , Tertiary Care Centers , Treatment Outcome
6.
JNMA J Nepal Med Assoc ; 57(219): 367-370, 2019.
Article in English | MEDLINE | ID: mdl-32329467

ABSTRACT

INTRODUCTION: Patient satisfaction is an important component of quality nursing care and is often determined by the nursing care in any health institution. The aim of the study is to find the presence of satisfaction among in-ward patients of five major wards at a tertiary care hospital regarding the quality of care provided by nursing staff. METHODS: A descriptive cross-sectional study was conducted among 105 patients of Patan Hospital from 3rd July to 3rd August, 2015 after obtaining ethical clearance from Institutional Review Committee. Sample size was calculated and stratified random sampling was done. Data was collected in Microsoft Excel and analyzed in Sta 13.0. Point estimate at 95% Confidence Interval was calculated and frequency and percentage was calculated for binary data. Subgroup analysis was done on the basis of demographic variables. RESULTS: Among 105 patients, 99 (94.3%) [94.93-95.07 at 95%CI] were satisfied with the nursing care provided at a tertiary care center in Nepal. Among them, 60 (60.6%) were females and 39 (39.4%) were males. Age of the patients ranged from 1 year to 85 years. The length of the stay in the hospital ranged from 2 to 17 days (mean = 5.6 days). CONCLUSIONS: Most of the patients were satisfied with the nursing care provided in a tertiary care centre. Routine nursing care surveys and immediate feedbacks would keep the authorities updated and deliver good health care.


Subject(s)
Nursing Staff, Hospital/standards , Patient Satisfaction/statistics & numerical data , Quality of Health Care , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Delivery of Health Care/standards , Female , Humans , Infant , Length of Stay , Male , Middle Aged , Nepal , Tertiary Care Centers/standards , Young Adult
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